CN102603646B - Synthesis method of 4-[4-(methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazole - Google Patents
Synthesis method of 4-[4-(methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazole Download PDFInfo
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- FZGSSCBBLPSBGU-UHFFFAOYSA-N 5-(4-methylsulfonylphenyl)-4-phenyl-2-(trifluoromethyl)-1h-imidazole Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)NC(C(F)(F)F)=N1 FZGSSCBBLPSBGU-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000001308 synthesis method Methods 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- 229940095102 methyl benzoate Drugs 0.000 claims abstract description 9
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 claims abstract description 9
- GWTBCUWZAVMAQV-UHFFFAOYSA-N 2,2,2-trifluoro-1-methoxyethanol Chemical compound COC(O)C(F)(F)F GWTBCUWZAVMAQV-UHFFFAOYSA-N 0.000 claims abstract description 8
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012346 acetyl chloride Substances 0.000 claims abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 79
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 54
- 125000005594 diketone group Chemical group 0.000 claims description 36
- 238000003756 stirring Methods 0.000 claims description 30
- 239000012043 crude product Substances 0.000 claims description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 19
- 238000001035 drying Methods 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- 239000003960 organic solvent Substances 0.000 claims description 18
- FTJGECIARDVRJC-UHFFFAOYSA-N 1-(4-methylsulfanylphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(SC)C=C1 FTJGECIARDVRJC-UHFFFAOYSA-N 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 238000000605 extraction Methods 0.000 claims description 15
- 229910002027 silica gel Inorganic materials 0.000 claims description 15
- 239000000741 silica gel Substances 0.000 claims description 15
- 229960001866 silicon dioxide Drugs 0.000 claims description 15
- 239000012074 organic phase Substances 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 10
- 238000001953 recrystallisation Methods 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 239000012046 mixed solvent Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 7
- 239000005695 Ammonium acetate Substances 0.000 claims description 7
- 229940043376 ammonium acetate Drugs 0.000 claims description 7
- 235000019257 ammonium acetate Nutrition 0.000 claims description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 6
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 6
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 5
- 239000010813 municipal solid waste Substances 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 239000012047 saturated solution Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 claims description 5
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 abstract description 6
- 239000012286 potassium permanganate Substances 0.000 abstract description 4
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 abstract description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract description 3
- 230000006378 damage Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- JECUZQLBQKNEMW-UHFFFAOYSA-N 1-(4-methylsulfanylphenyl)ethanone Chemical compound CSC1=CC=C(C(C)=O)C=C1 JECUZQLBQKNEMW-UHFFFAOYSA-N 0.000 abstract 2
- 230000001590 oxidative effect Effects 0.000 abstract 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 abstract 1
- 239000012414 tert-butyl nitrite Substances 0.000 abstract 1
- 238000004809 thin layer chromatography Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 10
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 7
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 229960001701 chloroform Drugs 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 230000005494 condensation Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 238000007239 Wittig reaction Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- UOHBMRODJBFDPN-UHFFFAOYSA-N C(C)(C)(C)O.[Li] Chemical compound C(C)(C)(C)O.[Li] UOHBMRODJBFDPN-UHFFFAOYSA-N 0.000 description 1
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- -1 glyoxaline compound Chemical class 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000007180 physiological regulation Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a novel synthesis method of 4-[4-(methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazole and belongs to the technical field of organic chemical synthesis. The method comprises the following steps: carrying out reaction on thioanisole and acetyl chloride to generate 4-methylthioacetophenone, carrying out reaction on 4-methylthioacetophenone and methyl benzoate to generate 1-(4-methylthiophenyl)-3-phenyl-1,3-dione, carrying out reaction on 1-(4-methylthiophenyl)-3-phenyl-1,3-dione and tert-butyl nitrite to generate 1-(4-methylthiophenyl)-2-phenyl-1,2-dione, carrying out reaction on 1-(4-methylthiophenyl)-2-phenyl-1,2-dione and trifluoroacetaldehyde methyl hemiacetal to generate 4-[4-(methylthio)phenyl]-5-phenyl-2-(thrifluoromethyl)-1H-imidazole, and finally oxidizing to generate 4-[4-(methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazole. According to the invention, the synthesis method is adopted, the utilization of cyanide and the damage of KMnO4 to carbon-carbon double bond are avoided, so that the method has industrial application values.
Description
Technical field
The present invention relates to organic chemical synthesis technical field, is specifically related to a kind of synthetic 4-[4-(methylsulfonyl) phenyl] method of-5-phenyl-2-(trifluoromethyl)-1H-imidazoles.
Background technology
Prostaglandin(PG) is being played the part of important role in the production process of inflammation, and the generation that suppresses prostaglandin(PG) is a Basic Ways of anti-inflammatory action.But common NSAID (non-steroidal anti-inflammatory drug), in usually stoping inflammation by inhibition prostate gland, has also suppressed the normal physiological regulation process of prostaglandin(PG).Therefore the use of high dosage antiphlogiston can cause side effect, especially serious ulcer.The action pathway of traditional NSAID (non-steroidal anti-inflammatory drug) is to stop inflammation by suppressing a kind of enzyme cyclooxygenase (COX) relevant with the generation of prostaglandin(PG).
Research shows to replace COX can reach more efficiently the object and the less (Proc.Natl.Acad.Sci of side effect that stop inflammation by suppressing another kind of enzyme cyclooxygenase II (COX II), USA, 89,7384 (1992)).People (the U.s.Pat.No.5 such as Richard M.Weier, 620,999) imidazole derivative is found in research, the structural formula of this imdazole derivatives is suc as formula shown in (1), this imdazole derivatives can high-level efficiency highly selective inhibition COX II, and COX is had to less restraining effect.The wherein IC to COX II
50be less than 0.2 μ M, selectivity is higher than 100.
The synthetic method of such glyoxaline compound of report has following several (U.s.Pat.No.5,620,999 at present; Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors Bioorganic & Medicinal Chemistry Letters 8 (24): 3443-3448 :)
(1) close ring-oxidising process through condensation-oxidation-condensation.This approach has met early stage needs, but benzoic condensation one step, poor repeatability, is difficult to amplify, and in hydrolytic process, produces hypertoxic HCN, and its reaction process is suc as formula shown in (2).
(2) through wittig reaction, two-step oxidation, last condensation is closed ring and is obtained final product.In this reaction scheme, to use KMnO
4, easily causing the fracture of carbon-carbon double bond, its reaction process is suc as formula shown in (3).
This reaction path is roughly the same with (2), and difference is that a step both sides substrate is exchanged in wittig reaction, and same, the shortcoming of this route is also KMnO
4easily cause the fracture of carbon-carbon double bond, its reaction process is suc as formula shown in (4).
In a word, above-mentioned three kinds of methods have shortcoming separately.A kind of front method is in benzoic condensation one step, and reaction poor repeatability, is difficult to amplify, and in hydrolytic process, produces hypertoxic HCN, limited the method application; Latter two method is being used KMnO
4when oxidation, may cause the fracture of carbon-carbon double bond.
Summary of the invention
The invention provides a kind of synthetic 4-[4-(methylsulfonyl) phenyl] method of-5-phenyl-2-(trifluoromethyl)-1H-imidazoles; 1; 3 diketone are converted into 1,2 diketone under the effect of cheap iron catalyst, have avoided use and the KMnO of prussiate
4destruction, have industrial applications be worth.
A kind of synthetic 4-[4-(methylsulfonyl) phenyl] method of-5-phenyl-2-(trifluoromethyl)-1H-imidazoles, comprising:
(1) under catalyst action, thioanisole and excess acetyl chloride generate 4-methylthio phenyl ethyl ketone, and described thioanisole and the mol ratio of catalyzer are 1: 1.1~3, are preferably 1.1~2.5, and the mol ratio of thioanisole and Acetyl Chloride 98Min. is 1: 0.5~2;
(2) under catalyst action, described 4-methylthio phenyl ethyl ketone reacts with methyl benzoate and generates 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone, described 4-methylthio phenyl ethyl ketone and catalyst molar ratio are 1: 2~4, and the mol ratio of 4-methylthio phenyl ethyl ketone and methyl benzoate is 1: 0.5~2;
(3) under catalyst action, described 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone and nitrite tert-butyl reaction generate 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone, described 1-(4-methylthio phenyl)-3-phenyl-1, the mol ratio of 3 diketone and catalyzer is 1: 0.1~0.5,1-(4-methylthio phenyl)-3-phenyl-1, and the mol ratio of 3 diketone and nitrite tert-butyl is 1: 3~7;
(4) described 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone react with ammonium acetate and trifluoro acetaldehyde methyl hemiacetal and generate 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles, described 1-(4-methylthio phenyl)-3-phenyl-1, the mol ratio of 2 diketone and trifluoro acetaldehyde methyl hemiacetal is 1: 1.1~2,1-(4-methylthio phenyl)-3-phenyl-1, the mol ratio of 3 diketone and ammonium acetate is 1: 1.1~4, is preferably 1.1~3;
(5) described 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles generates described 4-[4-(methylsulfonyl) phenyl after oxygenant oxidation]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles, described 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles and oxygenant mol ratio be 1: 1.8~2.2.
Catalyzer described in step (1) is aluminum chloride, iron trichloride or zinc dichloride, and reaction is carried out in the organic solvents such as methylene dichloride, trichloromethane or dithiocarbonic anhydride; When temperature of reaction is too low, reaction not exclusively, when temperature of reaction is too high, has impurity to produce in product, all affects the productive rate of product, and therefore, preferred as one, the temperature of reaction in step (1) is 10~30 ℃; Reaction times is not very large on the impact of productive rate, generally will the reaction times be controlled at 10-20 hour, is all that reaction is spent the night in general situation, in 10-20 hour, all can.
Catalyzer described in step (2) is sodium hydride, sodium tert-butoxide, potassium tert.-butoxide or trimethyl carbinol lithium, is preferably hydrogenation and receives, and reaction is carried out in tetrahydrofuran (THF) or DMF; When temperature of reaction is too low, reaction not exclusively, when temperature of reaction is too high, has impurity to produce in product, all affects the productive rate of product, and therefore, preferred as one, the temperature of reaction in step (2) is 50~70 ℃; Reaction times is 10-20 hour, is all that reaction is spent the night in general situation, in 10-20 hour, all can.
Catalyzer described in step (3) is iron trichloride, ferric bromide, iron protochloride or ferric oxide; When temperature of reaction is too low, reaction not exclusively, when temperature of reaction is too high, has impurity to produce in product, all affects the productive rate of product, and therefore, preferred as one, the temperature of reaction in step (3) is 20-40 ℃; Reaction times is 10-20 hour, is all that reaction is spent the night in general situation, in 10-20 hour, all can.
Reaction described in step (4) is carried out in acetic acid; When temperature of reaction is too low, reaction not exclusively, when temperature of reaction is too high, has impurity to produce in product, all affects the productive rate of product, and therefore, preferred as one, the temperature of reaction in step (4) is 90-110 ℃; Reaction times is 10-20 hour.
The reaction of step (5) is carried out in methylene dichloride or trichloromethane, described oxygenant is metachloroperbenzoic acid, hydrogen peroxide, peracetic acid or potassium permanganate, be preferably hydrogen peroxide, while oxidation, can not relate to carbon-carbon double bond herein, so can adopt potassium permanganate, oxidation is carried out under condition of ice bath, and oxidization time is 30-60min.
The detailed process of above step (1)~(5) is as follows:
(1) make solvent with methylene dichloride (DCM), trichloromethane or dithiocarbonic anhydride etc., in the time of 0~20 ℃, add thioanisole and catalyzer, under agitation condition, drip Acetyl Chloride 98Min., after dropwising, be warming up to room temperature (10~30 ℃), stir 10-20 hour; After completion of the reaction, add trash ice to reaction solution, drip concentrated hydrochloric acid to pH1~3, under room temperature, stir 15min, with dichloromethane extraction, organic phase washes with water successively, saturated common salt washing, except the mixed solvent recrystallization of sherwood oil and ethyl acetate for desolventizing gained crude product, obtain intermediate 4-methylthio phenyl ethyl ketone;
(2) make solvent with tetrahydrofuran (THF) or DMF, add catalyzer, stir after 10 minutes, add methyl benzoate, drip 4-methylthio phenyl ethyl ketone, after dropwising, be warming up to 50~70 ℃, stir 10-20 hour.After completion of the reaction, drip water, then add rare HCl to be adjusted to pH2~4, CH
2cl
2extraction, anhydrous sodium sulfate drying, except desolventizing gained crude product silicagel column purifying (sherwood oil: ethyl acetate=50: 1), obtain intermediate 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone;
(3) to catalyzer and 1-(4-methylthio phenyl)-3-phenyl-1, in the mixture of 3 diketone, add nitrite tert-butyl (TBN), at 20-40 ℃, stir 10-20 hour, after completion of the reaction, filter, except desolventizing gained crude product silicagel column purifying (sherwood oil: ethyl acetate=40: 1), obtain intermediate 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone, wherein nitrite tert-butyl can be easy to prepare by the trimethyl carbinol and Sodium Nitrite industrial;
(4) take acetic acid as solvent, add 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone, trifluoro acetaldehyde methyl hemiacetal and ammonium acetate, in 90-110 ℃ of reaction 10-20 hour, after completion of the reaction, add saturated Na
2cO
3solution regulates pH8~10, be extracted with ethyl acetate again, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, except desolventizing gained crude product with silicagel column purify (sherwood oil: ethyl acetate=5: 1), obtain intermediate 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles;
(5) take methylene dichloride as solvent, add 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles, at 0 ℃, drip wherein oxygenant as the dichloromethane solution of metachloroperbenzoic acid (mCPBA), after dropwising, continue to stir 30-60min under condition of ice bath, add the saturated solution of Sulfothiorine, with dichloromethane extraction, anhydrous sodium sulfate drying, on Rotary Evaporators, revolve except organic solvent, gained crude product MeOH recrystallization, obtaining white solid is end product 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles.
The reaction process of synthetic method of the present invention represents suc as formula shown in (5) with chemical equation, wherein in step (1) catalyzer used take aluminum chloride as example, catalyzer used in step (2) is received as example with hydrogenation, catalyzer used in step (3) is take iron trichloride as example, and oxygenant used in step (5) is take metachloroperbenzoic acid as example:
Beneficial effect of the present invention:
(1) yield is high, and cost is low, uses cheap raw material and catalyzer;
(2) avoided the generation of hypertoxic prussiate, more friendly to environment;
(3) prepare 1,2-diketone by 1,3-diketone, avoided strong oxidizer KMnO
4to the destruction of carbon-carbon double bond, by product is few.
Embodiment
Productive rate in all embodiment is all take the few substrate of molar weight as benchmark below
Embodiment 1
Synthesizing of step 1 4-methylthio phenyl ethyl ketone
In 250mL round-bottomed flask, add thioanisole (25g, 200mmol) and methylene dichloride (150mL); Under 0 ℃ of agitation condition, add wherein aluminum chloride (40g, 300mmol), then slowly drip Acetyl Chloride 98Min. (16g, 15mL, 200mmol); After dropwising, naturally rise to room temperature, stir 12 hours.After TLC (thin-layer chromatography) shows that reaction finishes, by reaction solution impouring trash ice, then add concentrated hydrochloric acid to adjust pH to 2 left and right.Under room temperature, stir 15min, use dichloromethane extraction three times, merge organic phase.Organic phase washes with water successively, saturated common salt washing, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, the mixed solvent recrystallization of sherwood oil and ethyl acetate for gained crude product, obtains white solid 4-methylthio phenyl ethyl ketone 20g, productive rate 60%.
1H?NMR(400MHz,CDCl
3,TMS):δ7.87(d,2H,J=8.8Hz),7.27(d,2H,J=8.8Hz),2.57(s,3H),2.52(s,3H);
13C?NMR(125MHz,CDCl
3,TMS)197.0,145.8,133.4,128.6,124.8,26.3,14.6.
Step 2 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone synthetic
In 250mL single port flask, add sodium hydride (60%1.8g 45mmol) and dry tetrahydrofuran (THF) (30mL); Under ice bath, stir after 10min, add methyl benzoate (2.7g 19.8mmol), and then drip 4-methylthio phenyl ethyl ketone (3g 18mmol); After dropwising, be warming up to 60 ℃, stir 12 hours.After TLC shows and reacts completely, to dripping the shrend reaction of going out in this reaction system, then add dilute hydrochloric acid to be adjusted to about pH3, dichloromethane extraction three times, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent gained crude product silicagel column purifying (sherwood oil: ethyl acetate=50: 1), obtain yellow solid 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone 3.1g, productive rate 63%.
1H?NMR(400MHz,CDCl
3,TMS):δ16.93(s,1H),7.97-7.99(m,2H),7.91(d,2H,J=8.4Hz),7.55(t,1H,J=7.6Hz),7.49(t,2H,J=7.6Hz),7.30(d,2H,J=8.0Hz),6.82(s,1H),2.54(s,3H);
13C?NMR(125MHz,CDCl
3,TMS):δ185.4,184.9,145.1,135.4,132.3,131.6,128.6,127.4,127.0,125.2,92.6,14.8.
Step 3 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone synthetic
In test tube, add iron trichloride (128mg, 0.8mmol), 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone (1.1g, 4mmol) and nitrite tert-butyl (2g, 19mmol), stir 12 hours in 30 ℃.After TLC demonstration reacts completely, diatomite filtration, is spin-dried for solvent, gained crude product silicagel column purifying (sherwood oil: ethyl acetate=40: 1), obtain yellow solid 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone 768mg, productive rate 74%.
1H?NMR(400MHz,CDCl
3,TMS):δ7.96(dd,2H,J=8.4,1.2Hz),7.87(d,2H,J=8.4Hz),7.65(t,1H,J=7.6Hz),7.50(t,2H,J=7.6Hz),7.28-7.30(m,2H),2.52(s,3H);
13C?NMR(125MHz,CDCl
3,TMS):194.5,193.4,148.9,134.7,133.0,130.0,129.8,129.1,128.9,125.0,14.5.
Step 4 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles synthetic
In 25mL round-bottomed flask, add 1-(4-methylthio phenyl)-3-phenyl-1,2 diketone (512mg, 2mmol), trifluoro acetaldehyde methyl hemiacetal (572mg, 4mmol), ammonium acetate (462mg, 6mmol) and acetic acid (5mL), 110 ℃ are refluxed 12 hours.After TLC demonstration reacts completely, add saturated Na
2cO
3solution is adjusted to pH9 left and right, and ethyl acetate extraction, merges organic phase, saturated common salt water washing, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, gained crude product silicagel column purifying (PE: EA=5: 1), obtain white solid 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 370mg, productive rate 55%.
1H?NMR(400MHz,DMSO-d6,TMS):δ13.84(br,1H),7.23-7.55(m,9H),2.56(s,3H);MS(EI,M/e):334。
Step 5 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles synthetic
At 0 ℃, to 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles (167mg, in methylene dichloride (10mL) solution 0.5mmol), drip metachloroperbenzoic acid (75%, 241mg, 1.05mmol) methylene dichloride (10mL) solution; After dropwising, continue to stir 30min under condition of ice bath, add the saturated solution of Sulfothiorine; With dichloromethane extraction three times, anhydrous sodium sulfate drying; On Rotary Evaporators, revolve except organic solvent, gained crude product MeOH recrystallization, obtains white solid 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 158mg, productive rate 86%.
1H?NMR(400MHz,DMSO-d6,TMS):δ14.00(br,1H),7.49-7.73(m,9H),2.76(s,3H),MS(ESI,(M-H)
-):364.9.。
Embodiment 2
Synthesizing of step 1 4-methylthio phenyl ethyl ketone
In 250mL round-bottomed flask, add thioanisole (25g, 200mmol) and methylene dichloride (150mL); Under 0 ℃ of agitation condition, add wherein iron trichloride (80g, 500mmol), then slowly drip Acetyl Chloride 98Min. (32g, 30mL, 400mmol); After dropwising, naturally rise to room temperature, stir 12 hours.After TLC shows that reaction finishes, by reaction solution impouring trash ice, then add concentrated hydrochloric acid to adjust pH2 left and right.Under room temperature, stir 15min, use dichloromethane extraction three times, merge organic phase.Organic phase washes with water successively, saturated common salt washing, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, the mixed solvent recrystallization of sherwood oil and ethyl acetate for gained crude product, obtains white solid 4-methylthio phenyl ethyl ketone 14g, productive rate 42%.
Step 2 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone synthetic
In 250mL single port flask, add sodium hydride (60%, 1.4g, 36mmol) and dry tetrahydrofuran (THF) (30mL).Under ice bath, stir after 10min, add methyl benzoate (1.2g, 9mmol), and then drip 4-methylthio phenyl ethyl ketone (3g, 18mmol); After dropwising, be warming up to 60 ℃, stir 12 hours.After TLC shows and reacts completely, to dripping the shrend reaction of going out in this reaction system, then add dilute hydrochloric acid to be adjusted to about pH3, dichloromethane extraction three times, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, gained crude product silicagel column purifying (sherwood oil: ethyl acetate=50: 1), obtain yellow solid 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone 1.8g, productive rate 74% (the substrate methyl benzoate few with respect to molar weight).
Step 3 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone synthetic
In test tube, add iron protochloride (51mg, 0.4mmol), 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone (1.1g, 4mmol) and nitrite tert-butyl (1.2g, 12mol), stir 12 hours in 30 ℃.After TLC demonstration reacts completely, diatomite filtration, is spin-dried for solvent, gained crude product silicagel column purifying (sherwood oil: ethyl acetate=40: 1), obtain yellow solid 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone 531mg, productive rate 51%.
Step 4 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles synthetic
In 25mL round-bottomed flask, add 1-(4-methylthio phenyl)-3-phenyl-1,2 diketone (512mg, 2mmol), trifluoro acetaldehyde methyl hemiacetal (314mg, 2.2mmol), ammonium acetate (127mg, 2.2mmol) and acetic acid (5mL), 110 ℃ are refluxed 12 hours.After TLC demonstration reacts completely, add saturated Na
2cO
3solution is adjusted to pH9 left and right, and ethyl acetate extraction, merges organic phase, saturated common salt water washing, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, gained crude product silicagel column purifying (PE: EA=5: 1), obtain white solid 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 290mg, productive rate 43%.
Step 5 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles synthetic
At 0 ℃, to 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles (167mg, in methylene dichloride (10mL) solution 0.5mmol), drip hydrogen peroxide (30%, 102mg, 0.9mmol) methylene dichloride (10mL) solution.After dropwising, continue to stir 30min under condition of ice bath, add the saturated solution of Sulfothiorine.With dichloromethane extraction three times, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, gained crude product MeOH recrystallization, obtains white solid 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 124mg, productive rate 68%.
Embodiment 3
Synthesizing of step 1 4-methylthio phenyl ethyl ketone
In 250mL round-bottomed flask, add thioanisole (25g, 200mmol) and trichloromethane (150mL); Under 0 ℃ of agitation condition, add wherein aluminum chloride (32g, 240mmol), then slowly drip Acetyl Chloride 98Min. (8g, 7.5mL, 100mmol); After dropwising, naturally rise to room temperature, stir 12 hours.After TLC shows that reaction finishes, by reaction solution impouring trash ice, then add concentrated hydrochloric acid to adjust pH2 left and right.Under room temperature, stir 15min, use dichloromethane extraction three times, merge organic phase.Organic phase washes with water successively, saturated common salt washing, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, the mixed solvent recrystallization of sherwood oil and ethyl acetate for gained crude product, obtains white solid 4-methylthio phenyl ethyl ketone 17g, productive rate 51%.
Step 2 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone synthetic
In 250mL single port flask, add sodium hydride (60%, 2.9g, 72mmol) and dry tetrahydrofuran (THF) (30mL); Under ice bath, stir after 10min, add methyl benzoate (4.9g, 36mmol), and then drip 4-methylthio phenyl ethyl ketone (3g, 18mmol); After dropwising, be warming up to 60 ℃, stir 12 hours.After TLC shows and reacts completely, to dripping the shrend reaction of going out in this reaction system, then add dilute hydrochloric acid to be adjusted to about pH3, dichloromethane extraction three times, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent gained crude product silicagel column purifying (sherwood oil: ethyl acetate=50: 1), obtain yellow solid 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone 3.1g, productive rate 63%.
Step 3 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone synthetic
In test tube, add ferric oxide (319mg, 2mmol), 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone (1.1g, 4mmol) and nitrite tert-butyl (2.9g, 28mmol), stir 12 hours in 30 ℃.After TLC demonstration reacts completely, diatomite filtration, is spin-dried for solvent, gained crude product silicagel column purifying (sherwood oil: ethyl acetate=40: 1), obtain yellow solid 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone 596mg, productive rate 57%.
Step 4 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles synthetic
In 25mL round-bottomed flask, add 1-(4-methylthio phenyl)-3-phenyl-1,2 diketone (512mg, 2mmol), trifluoro acetaldehyde methyl hemiacetal (429mg, 3mmol), ammonium acetate (385mg, 5mmol) and acetic acid (5mL), 110 ℃ are refluxed 12 hours.After TLC demonstration reacts completely, add saturated Na
2cO
3solution is adjusted to pH9 left and right, and ethyl acetate extraction, merges organic phase, saturated common salt water washing, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, gained crude product silicagel column purifying (PE: EA=5: 1), obtain white solid 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 335mg, productive rate 50%.
Step 5 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles synthetic
At 0 ℃, to 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles (167mg, in methylene dichloride (10mL) solution 0.5mmol), drip methylene dichloride (10mL) solution of potassium permanganate (172mg, 1.1mmol).After dropwising, continue to stir 30min under condition of ice bath, add the saturated solution of Sulfothiorine.With dichloromethane extraction three times, anhydrous sodium sulfate drying.On Rotary Evaporators, revolve except organic solvent, gained crude product MeOH recrystallization, obtains white solid 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 115mg, productive rate 63%.
Product in embodiment 2 and embodiment 3 in every step reactions steps all contrasts by TLC, is defined as consistent with every step reactions steps products therefrom corresponding in embodiment 1.
Claims (1)
1. synthetic 4-[4-(methylsulfonyl) phenyl] method of-5-phenyl-2-(trifluoromethyl)-1H-imidazoles, it is characterized in that, step is as follows:
(1) in 250mL round-bottomed flask, add thioanisole 25g and methylene dichloride 150mL; Under 0 ℃ of agitation condition, add wherein aluminum chloride 40g, then slowly drip Acetyl Chloride 98Min. 16g; After dropwising, naturally rise to room temperature, stir 12 hours, after TLC shows that reaction finishes, by reaction solution impouring trash ice, then add concentrated hydrochloric acid to adjust pH to 2 left and right, under room temperature, stir 15min, use dichloromethane extraction three times, merge organic phase; Organic phase washes with water successively, saturated common salt washing, and anhydrous sodium sulfate drying revolves except organic solvent on Rotary Evaporators, and the mixed solvent recrystallization of sherwood oil and ethyl acetate for gained crude product, obtains white solid 4-methylthio phenyl ethyl ketone 20g, productive rate 60%;
(2) to adding 60% sodium hydride 1.8g and dry tetrahydrofuran (THF) 30mL in 250mL single port flask; Under ice bath, stir after 10min, add methyl benzoate 2.7g, and then drip 4-methylthio phenyl ethyl ketone 3g; After dropwising, be warming up to 60 ℃, stir 12 hours; After TLC shows and reacts completely, to dripping the shrend reaction of going out in this reaction system, then add dilute hydrochloric acid to be adjusted to about pH3, dichloromethane extraction three times, anhydrous sodium sulfate drying; On Rotary Evaporators, revolve except organic solvent, gained crude product is purified with silicagel column, the sherwood oil that leacheate is 50:1: the mixed solvent of ethyl acetate, obtains yellow solid 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone 3.1g, productive rate 63%;
(3) in test tube, add iron trichloride 128mg, 1-(4-methylthio phenyl)-3-phenyl-1,3 diketone 1.1g and nitrite tert-butyl 2g, stir 12 hours in 30 ℃; After TLC demonstration reacts completely, diatomite filtration, is spin-dried for solvent, gained crude product silicagel column purifying, the sherwood oil that leacheate is 40:1: the mixed solvent of ethyl acetate, obtains yellow solid 1-(4-methylthio phenyl)-2-phenyl-1,2 diketone 768mg, productive rate 74%;
(4) in 25mL round-bottomed flask, add 1-(4-methylthio phenyl)-3-phenyl-1,2 diketone 512mg, trifluoro acetaldehyde methyl hemiacetal 572mg, ammonium acetate 462mg and acetic acid 5mL, 110 ℃ are refluxed 12 hours; After TLC demonstration reacts completely, add saturated Na
2cO
3solution is adjusted to pH9 left and right, and ethyl acetate extraction, merges organic phase, saturated common salt water washing, anhydrous sodium sulfate drying; On Rotary Evaporators, revolve except organic solvent, gained crude product silicagel column purifying, leacheate is the sherwood oil of 5:1: the mixed solvent of ethyl acetate, obtains white solid 4-[4-(methylthio group) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 370mg, productive rate 55%;
(5) at 0 ℃, to 4-[4-(methylthio group) phenyl] drip the 10mL dichloromethane solution of 75% metachloroperbenzoic acid 241mg in the 10mL dichloromethane solution of-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 167mg; After dropwising, continue to stir 30min under condition of ice bath, add the saturated solution of Sulfothiorine; With dichloromethane extraction three times, anhydrous sodium sulfate drying; On Rotary Evaporators, revolve except organic solvent, gained crude product MeOH recrystallization, obtains white solid 4-[4-(methylsulfonyl) phenyl]-5-phenyl-2-(trifluoromethyl)-1H-imidazoles 158mg, productive rate 86%.
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Title |
---|
Lehao Huang, et al.."Iron-Promoted C-C Bond Cleavage of 1,3-Diketones:A Route to 1,2-Diketones under Mild Reaction Conditions".《The Journal of Organic Chemistry》.2011,第76卷(第14期),5732-5737. * |
LehaoHuang et al.."Iron-Promoted C-C Bond Cleavage of 1 |
Medicinal Chemistry Letters》.1998,第8卷(第24期),3443-3448. * |
Thomas E.Barta, et al.."Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors".《Bioorganic & * |
ThomasE.Barta et al.."Antiinflammatory 4 |
张育川."间氯过氧化苯甲酸".《精细与专用化学品》.2004,第12卷(第7期),12-13. |
黄银华等."4-甲硫基苯乙酸的合成研究".《化学世界》.2005,(第11期),675-677. |
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